DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service

 

 National Institute for Occupational 

 Safety and Health 

 Robert A. Taft Laboratories

 4676 Columbia Parkway

 Cincinnati, OH 45226-1998

 Phone: 513-533-6825 

 Fax: 513-533-6826 

 

 

Dear ABRWH members, 

Notice of intent to change the NIOSH-IREP lung cancer risk model for estimating probability 

of causation under EEOICPA

As you know, there are two different versions of IREP. NIOSH-IREP is the version maintained by 

NIOSH. A separate version (NIH-IREP) is maintained by the National Cancer Institute (NCI.) 

NIH-IREP was developed primarily to serve the needs of the Department of Veterans Affairs in 

adjudicating cancer claims filed by veterans exposed to radiation during military service, whereas 

the risk models in NIOSH-IREP are intended to fit the characteristics and radiation exposures 

incurred by civilian nuclear weapons workers. 

Perhaps the most significant difference between NIOSH-IREP and NIH-IREP occurs in the 

treatment of lung cancer risk for exposure to radiation other than radon. Initially, these risk models 

were identical in the two versions of IREP. However, NCI revised the NIH-IREP lung model in late 

2003 based on both newly published and unpublished (1) data from the Japanese atomic bomb 

survivor cohort, including the incorporation of different assumptions about the interaction between 

cigarette smoking and lung cancer. 

This lung model revision was followed in mid-2004 by a modification to the NIH-IREP computer 

code for exposures to alpha radiation. NCI modified the computer code again in September 2005, 

this time to adjust the population transport function (the parameters that affect the transfer of risk 

from the Japanese population to the U.S. population) in the NIH-IREP lung risk model. The purpose 

of the 2004 and 2005 modifications was to ensure consistency with the NIH-IREP documentation 

(Report of the NCI-CDC Working Group to Revise the 1985 NIH Radioepidemiological Tables), 

published by NCI in 2003. Online links to the NCI report and to the NIH-IREP computer program 

are provided on the NIOSH/OCAS Web site: www.cdc.gov/niosh/ocas . (To access the NCI/NIH 

links, navigate to the “Probability of Causation—NIOSH-IREP” page and scroll down to the “Other 

Related Materials” section, located at the bottom of the page.)

In the revised NIH-IREP lung model, risk is adjusted for age at exposure and age at diagnosis. The 

NIOSH-IREP lung model does not adjust for these age-dependent factors. Further, the NIH-IREP 

lung model relies less on a multiplicative interaction than does NIOSH-IREP in accounting for the 

interaction between cigarette smoking and lung cancer. Consequently, the same inputs entered into 

NIH-IREP and NIOSH-IREP produce substantially different probabilities of causation for some 

exposure profiles. In terms of probability of causation, the main effect of the NCI revisions is that 

NIH-IREP is more favorable to smokers and NIOSH-IREP is more favorable to non-smokers. Other 

effects (age and gender-related, for example) vary in accordance with the circumstances of a case 

and are more difficult to generalize. 
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We began evaluating the new NIH-IREP lung model in 2004 for its applicability to workers covered 

under EEOICPA. To assist with this evaluation, SENES Oak Ridge, Inc. provided NIOSH with a 

detailed assessment of the differences between the two IREP lung models (2). The SENES 

assessment concluded with a recommendation to replace the NIOSH-IREP lung model with the new 

NIH-IREP model or, alternatively, to consider programming NIOSH-IREP to run both models. (In 

the latter option, the higher probability of causation would determine the claim outcome.) 

To help resolve this issue, we obtained input from four outside experts, posing the following 

question to each: “In your expert scientific judgment, should NIOSH adopt the NIH-IREP lung 

cancer risk model for exposures other than radon for use in NIOSH-IREP? If so, should the model 

be adopted intact, or should NIOSH modify it in some way to better fit the characteristics and 

radiation exposures of nuclear weapons workers covered under EEOICPA? Alternatively, should 

NIOSH-IREP be programmed to run both lung cancer models and to report only the higher 

probability of causation? Please provide the rationale for your conclusion.” (3) 

The four experts recruited by NIOSH are: David J. Brenner, PhD, Professor of Radiation Oncology 

and Public Health, Columbia University School of Public Health; Faith G. Davis, PhD, Professor of 

Epidemiology and Biostatistics, University of Illinois at Chicago, School of Public Health; David B. 

Richardson, PhD, Assistant Professor of Epidemiology, University of North Carolina School of 

Public Health; and Jonathan M. Samet, MD, MS, Professor and Chairman, Department of 

Epidemiology, Johns Hopkins University School of Public Health. 

Each expert reviewed the question independently of the other reviewers. Faith Davis recommended 

adopting the NIH-IREP model, noting that since it is based on more recent evidence, it represents an 

improvement over the current NIOSH-IREP model (4). Jonathan Samet and David Richardson, 

concluding that the evidence is not compelling enough to support the exclusive use of either model, 

recommended that we run both models and use the higher probability of causation (5, 6). David 

Brenner argued that the state of knowledge remains inconclusive with respect to the interaction 

between smoking and external radiation, and recommended modifying NIH-IREP by introducing 

alternate interaction assumptions (7). SENES prepared a detailed analysis and summary of the four 

expert opinions (8). That report and all other documents referenced in this letter are enclosed. 

Perhaps the only real consensus among the four reviewers is that none recommends the exclusive 

retention of the NIOSH-IREP model. Also striking is the diversity of opinion as to how to properly 

characterize and model the interaction between cigarette smoking and radiation. NIOSH recognizes 

that the NIH-IREP lung risk model utilizes additional years of follow-up of the Japanese survivor 

cohort, but also notes the substantive points raised by our expert reviewers. Thus, we conclude that 

the current state of scientific knowledge of this issue is ambiguous, and that there are sufficient 

reservations about the NIH-IREP model to justify an alternative approach. 

After considerable evaluation and discussion, we propose to program NIOSH-IREP to run both lung 

cancer risk models and to report only the higher probability of causation. A notice to this effect will 

be included in the Federal Register notice for the October 2005 ABRWH meeting. NIOSH will fully 

brief the Board at this upcoming meeting, and will make no change to NIOSH-IREP until the Board 
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has considered the proposal and provided input. Should this change be implemented, all previous 

non-compensable lung cancer claims would be reevaluated. 

Sincerely, 

Larry J. Elliott, MSPH, CIH 

Director 

Office of Compensation 

 Analysis and Support 

cc: 

L. Wade 

L. Shields 

Enclosures: 

(1) Land CE and Pierce DA. Likelihood profile for parameter alpha used in computation of 

statistical uncertainty for ERR/Sv in NIH-IREP lung cancer model. Personal communication from 

Charles Land, NIH/NCI, to NIOSH, February 3, 2004. 

(2) Apostoaei AI and Trabalka JR, SENES Oak Ridge, Inc. Differences in the estimation of lung 

cancer risk between NIOSH-IREP and NIH-IREP. September 20, 2004. 

(3) NIOSH/OCAS. Evaluation of NIH-IREP lung cancer risk model for application to NIOSH-IREP. 

(Instructions and summary of IREP lung model evaluation provided by NIOSH to outside experts), 

undated; E-mailed to reviewers on November 26, 2004. 

(4) Davis FG. Response to NIOSH questions. Expert opinion solicited by NIOSH, February 10, 

2005. 

(5) Samet, JM. Evaluation of two models for projecting lung cancer risk: NIOSH-IREP and NIHIREP. Expert opinion solicited by NIOSH, February 22, 2005. 

(6) Richardson DB. Should NIOSH adopt the NIH-IREP model for lung cancer for use in the 

EEOICPA? Expert opinion solicited by NIOSH, February 28, 2005 

(7) Brenner DJ. Lung Cancer: Interaction of radiation exposure with smoking. What to do in IREP? 

Expert opinion solicited by NIOSH, June 28, 2005. 

(8) SENES Oak Ridge, Inc. How should NIOSH estimate risk of lung cancer in workers covered 

under EEOICPA in the face of uncertainties in the interaction between smoking and low-LET 

radiation. (Analysis and summary of expert opinions),